Submissions for variant NM_001243133.2(NLRP3):c.208G>A (p.Val70Met)

gnomAD frequency: 0.00031  dbSNP: rs117287351

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000757572	SCV000292541	likely benign	not provided	2021-02-02	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 28028683, 23633568, 31172726, 28956000, 31664448, 33329557, 32115236)
Illumina Laboratory Services, Illumina	RCV000269968	SCV000356905	likely benign	Chronic infantile neurological, cutaneous and articular syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000327334	SCV000356906	likely benign	Familial amyloid nephropathy with urticaria AND deafness	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000384324	SCV000356907	likely benign	Familial cold autoinflammatory syndrome 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae	RCV001079905	SCV000767336	benign	Cryopyrin associated periodic syndrome	2024-01-25	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757572	SCV000885861	uncertain significance	not provided	2017-06-08	criteria provided, single submitter	clinical testing	The NLRP3 c.214G>A;p.Val72Met variant has been listed in the medical literature in at least two individuals with autoinflammatory disease (Nakayama 2017). The variant is listed in the ClinVar database (Variation ID: 245593) and in the dbSNP variant database (rs117287351) with an allele frequency of up to 0.9 percent (171/18868 alleles) in East Asians in the Genome Aggregation Database. The amino acid at this position is conserved across species and computational algorithms (PolyPhen2, SIFT) predict this variant is deleterious. Considering available information, the clinical significance cannot be determined with certainty. If this variant is later determined to be pathogenic, this individual is predicted to be affected with autosomal dominant CINCA syndrome, Familial cold-induced inflammatory syndrome, or Muckle-Wells syndrome (OMIM#606416). References: Nakayama M et al. Accurate clinical genetic testing for autoinflammatory diseases using the next-generation sequencing platform MiSeq. Biochem Biophys Rep 2017 9:146-152.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000236962	SCV001365972	likely benign	not specified	2017-08-23	criteria provided, single submitter	clinical testing	p.Val72Met in exon 1 of NLRP3: This variant is not expected to have clinical significance because it has been identified in 0.81% (70/8600) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs117287351).
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002262849	SCV002543645	likely benign	Autoinflammatory syndrome	2021-03-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000757572	SCV004701053	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	NLRP3: BP4, BS1